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CD3 is the switch on every T cell. Bispecific drugs grab it with one arm and the tumour with the other, forcing the T cell to attack.
CD3 (gene CD3E) is the invariant signalling component of the T-cell receptor complex, and engaging it triggers T-cell activation and cytokine release independent of MHC presentation. It is found on all T cells and is therefore an effector handle rather than a tumour target. Every T-cell engager, including blinatumomab, teclistamab, tarlatamab, glofitamab and tebentafusp, uses an anti-CD3 arm to recruit any passing T cell to a tumour antigen bound by the other arm. Affinity tuning of the CD3 arm is the main lever on cytokine release syndrome, and step-up dosing is the standard clinical countermeasure. How much CD3 affinity, valency and format can be optimised to separate potency from toxicity is still being worked out. The plain version: bispecifics grab CD3 with one arm and the tumour with the other, forcing the T cell to attack.
In plain words · CD3 is the switch on every T cell. Bispecific drugs grab it with one arm and the tumour with the other, forcing the T cell to attack.
Backbone ribbon from PDB 12ES. RCSB PDB 12ES. The ribbon widens where the chain is folded into a regular pattern and narrows where it is a loose loop.
CD3 is the switch on every T cell. Bispecific drugs grab it with one arm and the tumour with the other, forcing the T cell to attack.
Invariant TCR co-receptor; engagement triggers activation and cytokine release independent of MHC.
24 products aim at CD3: bispecific antibodies and cell therapies. Because it sits on the outside of the cell, it can be reached from the bloodstream: antibodies flag the cell, ADCs deliver a toxin, radioligands deliver radiation, and CAR-T or bispecifics bring a T cell.
Immune or microenvironment target: its medicines act on immune, stromal or bone cells rather than on the tumour cell (drug mechanisms in the corpus). HPA CD3E: RNA tissue enriched (lymphoid tissue 596 nTPM); blood lineage group enriched (NK-cells 203 nTPM, T-cells 503 nTPM); high antibody staining in 3 normal tissues. Distribution: no corpus cancer carries a prevalence row, threshold or catalogue link for it; Open Targets associates it with 5 specific cancer types at or above 0.5 (plasma cell myeloma, diffuse large B-cell lymphoma, acute lymphoblastic leukemia, follicular lymphoma, small cell lung carcinoma). (Rule 1 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas CD3E tissue; UniProt P07766; Open Targets ENSG00000198851 associations
First described 1986. Earliest sequence paper UniProt cites for the protein: Gold D.P. et al, Nature, 1986, "Isolation of cDNA clones encoding the 20K non-glycosylated polypeptide chain of the human T-cell receptor/T3 complex". Source.
Invariant TCR co-receptor; engagement triggers activation and cytokine release independent of MHC.
RNA: tissue enriched (lymphoid tissue 596 nTPM), detected in many normal tissues. Blood: group enriched (NK-cells 203 nTPM, T-cells 503 nTPM).
Medium: Bone marrow, Spleen.
No cancer sample stained medium or high.
HPA CD3E tissue · HPA CD3E pathology · HPA protein class: CD markers, FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Metastatic cancer | immune% | Immune-cell target (CD3 on every T cell, the arm that T-cell engagers pull on): expressed on immune cells rather than on the tumour, so patient selection rests on the cancer type and, in trials, on PD-L1 or immune biomarkers. |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
ASP2138 is an experimental bispecific antibody from Astellas Pharma Global Development in phase 3 trials for gastric & gastro-oesophageal junction cancer, aimed at Claudin 18.2 and CD3.
AZD0486 is an experimental bispecific antibody from AstraZeneca in phase 3 trials for diffuse large B-cell lymphoma, aimed at CD19 and CD3.
AZD5863 is an experimental bispecific antibody from AstraZeneca in phase 2 trials for gastric & gastro-oesophageal junction cancer, pancreatic ductal adenocarcinoma and oesophageal cancer, aimed at Claudin 18.2 and CD3.
AZD6621 is an experimental T-cell engager from AstraZeneca in phase 2 trials for prostate cancer, aimed at CD3.
Blinatumomab was the first T-cell engager (2014), and is now given to children and adults with leukaemia even when in remission, because it improves survival.
Brenetafusp is a soluble T-cell receptor bispecific, tebentafusp's successor, that recognises a PRAME peptide on HLA-A*02:01 and drags T cells onto the tumour. A phase 3 with nivolumab in first-line melanoma is enrolling, but only patients carrying HLA-A*02:01, about half of those of European ancestry, are eligible.
CART84 is an experimental CAR-T cell therapy from Gyala Therapeutics in phase 2 trials for acute myeloid leukaemia, aimed at CD3.
Catumaxomab (Korjuny) is an antibody infused into the abdominal cavity to control malignant ascites, the build-up of fluid caused by cancers such as ovarian and stomach cancer, in people whose other treatments have stopped working.
Elranatamab is Pfizer's BCMA bispecific, given under the skin every week then every two weeks, for myeloma after four prior lines.
Epcoritamab is an under-the-skin injection that pulls T cells onto lymphoma cells; it is approved for relapsed large B-cell and follicular lymphoma, and moving toward first line.
Glofitamab is a fixed-duration bispecific for large B-cell lymphoma, with OS benefit when combined with chemotherapy.
Linvoseltamab is Regeneron's BCMA bispecific, approved in July 2025 with the highest complete-response rate of the class in its pivotal study.
M701 is Wuhan YZY Biopharma's EpCAM-CD3 bispecific antibody infused into the abdomen to control malignant ascites, in a phase 3 trial in China.
Mosunetuzumab is a fixed-duration CD20 bispecific approved for follicular lymphoma and studied with polatuzumab in large B-cell lymphoma.
Obrixtamig is an antibody with two arms: one grabs DLL3, a protein on the surface of most neuroendocrine carcinomas, and the other grabs a T cell, pulling the killer cell onto the cancer. It is in a phase 3 trial for neuroendocrine carcinomas outside the lung.
Odronextamab is Regeneron's CD20 bispecific, approved in Europe for lymphoma and in the US for follicular lymphoma after earlier FDA rejections over confirmatory-trial enrolment.
Pasritamig is Johnson & Johnson's bispecific T-cell engager that binds KLK2 on prostate cancer cells and CD3 on T cells, with a deliberately low-affinity CD3 arm. In phase 1 about 40% of patients had a PSA50 response with far less cytokine release syndrome than other engagers, and a phase 3 trial began in 2025.
Talquetamab is the first drug against GPRC5D, a second myeloma target used after BCMA therapies stop working; taste and skin side effects are its signature.
The first T-cell engager to improve survival in a common solid tumour, small-cell lung cancer.
The first drug to improve survival in metastatic uveal melanoma, and the first TCR-based bispecific.
Teclistamab was the first off-the-shelf bispecific for multiple myeloma, and is now approved after just one prior line of therapy.
TQB2825 is an experimental bispecific antibody from Chia Tai Tianqing Pharmaceutical in phase 2 trials for diffuse large B-cell lymphoma, aimed at CD20 and CD3.
Ubamatamab (REGN4018) is Regeneron's investigational MUC16×CD3 bispecific antibody, in phase 1/2 and phase 2 trials for ovarian and endometrial cancer.
Xaluritamig is Amgen's T-cell engager for prostate cancer, now in two phase 3 trials, aiming to do for prostate cancer what tarlatamab did for small-cell lung cancer.
AALL1731 brings immunotherapy into the front-line treatment of the commonest childhood cancer, in the group of children where most relapses were occurring despite good initial risk. Blinatumomab was approved for this use in 2024 and paediatric protocols worldwide are being amended. Whether it can allow less chemotherapy, and its effect on very low-risk children, are the next questions.
E1910 changed the standard of care for adult B-ALL: immunotherapy is now part of front-line consolidation even for patients with no detectable leukaemia, because MRD-negative by flow cytometry does not mean cured. It also demonstrated that a T-cell engager can improve overall survival in a curative setting. Chemotherapy-light or chemotherapy-free regimens built on blinatumomab and inotuzumab are the next step.
An off-the-shelf alternative to CAR-T for repeatedly relapsed follicular lymphoma: no apheresis, no manufacturing wait, and a complete response rate in the same range, at the cost of continued treatment rather than a single infusion.
Patients with small-cell lung cancer that has relapsed after chemotherapy now have a drug that works far better than topotecan or lurbinectedin, and it is the first T-cell engager approved for a solid tumour. Treatment requires inpatient monitoring for the first doses because of cytokine release syndrome, which most centres now manage on a short-stay basis. It does not yet apply to first-line treatment, where trials are ongoing.
CD20 x CD3 bispecifics gave patients whose lymphoma has failed CAR-T, or who cannot access it, an effective off-the-shelf treatment that can be started within days. Epcoritamab and glofitamab are now standard third-line options and are moving into earlier lines and combinations. They do not yet replace CAR-T, whose remissions appear more durable.
Elranatamab confirmed that BCMA bispecifics are a class, not a one-off, and its protocol-built dose reduction after response set a precedent for lowering the immunosuppressive burden of T-cell engagers. Patients now have two approved BCMA bispecifics and one against GPRC5D (talquetamab). Choosing between them, and sequencing them with CAR-T, remains guided by availability and toxicity profile rather than head-to-head data.
Teclistamab showed that an off-the-shelf bispecific can approach CAR-T-like response rates in late myeloma, giving patients who cannot wait for or access cell therapy a real option. It also exposed the price: prolonged T-cell engagement causes profound immunosuppression, so infection prophylaxis and immunoglobulin replacement are now routine. Less frequent dosing after response is being adopted to reduce this burden.
Query for this target: (TITLE:"CD3" OR ABSTRACT:"CD3" OR TITLE:"CD3E" OR ABSTRACT:"CD3E") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about CD3, not a curated reading list.
Shares Ajai Chari, MagnetisMM-3: elranatamab, a second BCMA bispecific, with a switch to fortnightly dosing after response, Talquetamab, T-cell engagers (bispecific) and the tag t-cell-engager-target.
Shares Harpoon Therapeutics, Obrixtamig, DeLLphi-301: tarlatamab, a DLL3-targeting T-cell engager, in previously treated small-cell lung cancer, Tarlatamab and the tag t-cell-engager-target.
Shares Pasritamig and the tag t-cell-engager-target.
Shares Xaluritamig and the tag t-cell-engager-target.
Shares Cullinan Therapeutics, Philippe Moreau, Linvoseltamab, Elranatamab and the tag t-cell-engager-target.
Shares Pasritamig, Xaluritamig, Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphoma, Elranatamab.
Shares TQB2825, Michael Dickinson, A Study to Assess the Anti-Tumor Activity and Safety of Odronextamab in Adult Patients With B-cell Non-Hodgkin Lymphoma Who Have Been Previously Treat, Catherine Thieblemont.
Shares Paul Nathan, IMCgp100-202, HLA-A, Tebentafusp.